the liver regenerative abilityIt can fully regrow even after two-thirds of its mass has been surgically removed. However, damage from medication, alcohol abuse, or obesity can eventually cause liver dysfunction.
Currently, the only effective treatments for end-stage liver disease are: transplant.
however, lack of available organs for transplantation.the patient may have to Wait 30 days to 5 years or more Receive a liver for transplant in the United States.of 11,600+ patients Just over 9,200 people on the waiting list to receive a liver transplant in 2021 have received a liver transplant.
But what if, instead of a liver transplant, there was a drug that helped the liver regenerate itself?
I Pittsburgh Liver Research Center run the lab Liver regeneration and cancer researchamong us recently published researchmy team and I have discovered that activating specific proteins with a new drug can promote regeneration and repair after severe liver injury or partial surgical resection in mice.
A key player in liver regeneration
the liver does Over 500 key features in your body, include It produces fat-carrying proteins in the body, converts excess glucose into glycogen for storage, and breaks down toxins such as ammonia.
Liver cells, or hepatocytes, undertake many of these tasks through a divide-and-conquer strategy. ZoningThis divides the liver into three zones with different roles, and by turning on specific genes activated in each zone, cells are instructed to perform specialized functions.
However, it is not well understood what exactly controls the expression of these genes.
For the past 20 years my team and other labs have Wnt Plays an important role in the control of liver function and regeneration.
Researchers know that Wnt proteins help activate repair processes in damaged liver cells, but which proteins actually control zoning and regeneration and their precise location within the liver. It remains a mystery whether
To identify these proteins and their origins, my team and I molecular mapping To identify where and how strongly 100 liver function genes are active.
we found it Only 2 of 19 Wnt genes, Wnt2 and Wnt9b were functionally present in the liver. We also found that Wnt2 and Wnt9b are localized to the endothelial cells lining blood vessels in zone 3 of the liver, an area involved in many metabolic functions.
Surprisingly, ablation of these two Wnt genes resulted in all hepatocytes expressing only genes normally restricted to zone 1, severely limiting overall liver function.
This finding suggests that hepatocytes are undergoing an ongoing push-and-pull of gene activation that can alter their function, and that Wnts are master regulators of this process.
Ablation of the two Wnt genes from endothelial cells also completely abolished hepatocyte division and regeneration after partial surgical excision of the liver.
Liver regeneration after Tylenol overdose
next, test for new drugs Helps restore liver zoning and regeneration. antibody It is called FL6.13 and shares similar functions with Wnt proteins, including activation of liver regeneration.
Over two days, the drug was administered to mice genetically engineered to lack Wnt2 and Wnt9b in liver endothelial cells. As a result, we were able to almost completely restore the division and repair functions of hepatocytes.
Finally, I wanted to test how effective this drug was in repairing the liver after a Tylenol overdose. heat and pain.
However, an overdose of Tylenol cause severe liver damageLiver failure and death may result if immediate medical attention is not sought. tylenol poisoning It is one of the most common causes of severe liver damage requiring liver transplantation in the United States.
Nonetheless, there is currently only one drug available to treat it, and it can only prevent liver damage if taken immediately after an overdose.
We tested the new drug in mice with liver injury from toxic doses of Tylenol. We know that death can be reduced.
These findings indicate that hepatocyte repair and tissue regeneration are occurring.
reduce the need for transplants
One way to address the liver transplant shortage is to improve treatments for liver disease. Although current drugs can effectively treat Hepatitis Cis a viral infection that causes inflammation of the liver, but other liver diseases have not seen the same progression.
With few effective treatments available for diseases such as non-alcoholic fatty liver disease and alcoholic liver disease, many patients deteriorate and eventually require a liver transplant.
My team and I believe that improving the liver’s ability to self-repair can help avoid the need for a transplant. may help reduce the burden of
SaddarshanmongaProfessor of Pathology and Medicine, University of Pittsburgh Health Sciences
This article is reprinted from conversation Under Creative Commons License.read Original work.
